ABBOTT PARK, Ill.—Abbott will collaborate with Merck to
evaluate the use of a fluorescence in-situ
hybridization (FISH)-based companion diagnostic test to aid in the development
of a Merck
investigational cancer therapy.

FISH-based companion diagnostic tests are designed to
identify
specific DNA sequences to help guide physicians in determining which
patients are more or less likely to benefit from a particular therapy. FISH
technology has a variety of uses, an Abbott spokesperson points out. It can
identify whether too many, or too few, copies of a particular gene are
present
or whether certain genes have rearrangements that play an active role in
disease progression.

"The use of FISH to determine genomic status and the link to
therapeutic outcome in oncology is one of the fastest-growing applications. In
this instance, a FISH assay will be developed to examine copy number of the
TP53 gene," she adds.

The Abbott FISH assay will be evaluated in clinical trials
to help identify patients more likely to respond favorably to Merck's as-yet
unidentified investigational cancer therapy.

Merck evaluated number of potential partners and Abbott was
chosen as a partner to develop this
companion diagnostic test.

"We have proven capabilities to take a product through the
regulatory
process, manufacturing, distribution and implementation in a
clinical lab setting," the Abbott spokesperson says.

Merck will be responsible for establishing the clinical
trial sites with regard to all aspects of patient recruitment and therapy
administration. Abbott Molecular will work with
Merck to select the FISH
testing labs, and then Abbott will provide assay training and monitor the
laboratory sites.

"Our goal through this collaboration, and others like it, is
to ensure that the right medicine gets to the right patient,"
says Stafford
O'Kelly, head of Abbott's molecular diagnostics business. "As one of the early
pioneers in companion diagnostics, we believe that
linking genetic testing with
drug development at the earliest stages can increase the effectiveness and
predictability of medicines and help physicians
make more informed treatment
decisions."

Abbott's portfolio of companion diagnostic tests
includes
the PathVysion HER-2 DNA Probe Kit, which represents one of the first examples
of innovations in the field of personalized medicine. The test
is approved for
use in selecting breast cancer patients for whom Herceptin (trastuzumab)
therapy is being considered. In addition, Abbott's Vysis ALK
Break Apart FISH
Probe kit was approved in 2011 for use in identifying non-small cell lung
cancer patients for Pfizer's XALKORI (crizotinib) treatment
in the United
States, Canada, South Korea, Japan and a number of other markets. Global
commercialization continues to progress as Xalkori and Vysis ALK
receive
additional individual country approvals, Abbott notes.

"Our collaboration with GSK was
expanded in November 2011.
The existing agreements focused on the development of PCR tests to screen
non-small cell lung cancer and melanoma tumors for
expression of the MAGE-A3
antigen. Under the expanded agreement, Abbott will develop a PCR test for use
on the Abbott m2000rt instrument, to screen
non-small cell lung cancer tumors
for the expression of the PRAME antigen. PRAME is a preferentially expressed
antigen of melanoma that is expressed in
69 percent of non-small cell lung
cancer cases, as well as in a wide variety of cancer types, including melanoma,
breast, ovarian and bladder cancer,
with limited expression in normal cells,"
the spokesperson tells ddn.

Abbott Molecular
is a leader in molecular diagnostics—the
analysis of DNA and RNA at the molecular level. Abbott Molecular's tests can
also detect subtle but key
changes in patients' genes and chromosomes and have
the potential for earlier detection or diagnosis, provide information relevant
to the selection of
appropriate therapies, and may improve monitoring of
disease progression.

In an unrelated
development, Abbott will collaborate with
Genetics Laboratory Inc. (GenLab) on the development of a molecular diagnostic
test that will be designed to
rapidly detect microorganisms that cause orthopedic
infections. Under terms of the agreement, Abbott, in conjunction with GenLab,
will develop and
commercialize the new assay for use on the PLEX-ID automated
microbial identification system. In the United States, PLEX-ID is currently
intended only
for non-diagnostic use, but assays are now being developed for
future clinical diagnostic uses.

PLEX-ID
has the ability to rapidly identify a broad variety
of microorganisms. The system is capable of generating results within five to
six hours in contrast
to other methods, which may take several days or longer
for positive identification.

"Bacteria,
particularly antibiotic-resistant species such as
MRSA, are very dangerous in orthopedic patients because the bacterial colonies
attach to the
artificial surfaces of the implants," says Dr. Gerhard Maale, an
orthopedic oncologic surgeon and an expert in orthopedic infections in the
Dallas-Ft.
Worth area.

Maale will also serve as the medical director for the
Abbott-GenLab collaboration.

"A molecular diagnostic test designed to detect
microorganisms that cause orthopedic infections, running on the
PLEX-ID, could
have the ability to determine which pathogens are responsible for an infection
while assessing the genetic composition and potentially
antibiotic resistance,"
Maale says. "This could be a major step forward in diagnosing and treating
serious infections in artificial joint recipients,
with the potential to
provide important information to physicians that they could use to save
treatment costs and improve the quality of life for these
patients."

According to the New England Journal of Medicine, about 800,000 knee and hip replacement procedures
are performed annually in the United States,
and complications related to
infections occur in approximately 2 percent of those procedures. In addition,
more than 70,000 joint revisions are
performed annually in the United States,
with greater than 15 percent of hip and 25 percent of knee revisions caused by
infections. Revisions are often
more expensive than the original procedure.

FISH:Navigating
the waters of personalized
medicine

PRETREATMENT: Cells
or
tissue are placed on a slide and treated (fixed) to stabilize cellular
structures. Chemical and enzymatic procedures are employed to remove membranes,
and cytoplasmic proteins that prevent access to the cells' DNA.

DENATURATION: Cell
DNA is exposed to high temperature in order to open the DNA, making it
accessible to fluorescent-labeled probe DNA.

HYBRIDIZATION: Probe
is added to the sample and allowed to combine with complementary
sequence of
the target DNA.

WASHING: Excess
probe is removed
post-hybridization, and a counterstain is applied to visualize
the individual cells and nuclei.

FISH can utilize more than one fluorescent label at one time
to be able to detect multiple genes (or gene loci) in a single hybridization.
Colors are counted or enumerated to determine the gene status, amplification,
deletion and translocation.